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在大鼠中,多次皮下注射生长抑素会导致对血浆胰岛素抑制作用的快速耐受性,但对胰高血糖素的抑制作用则不会。

Multiple subcutaneous injections of somatostatin induce tachyphylaxis of the suppression of plasma insulin, but not glucagon, in the rat.

作者信息

Märki F, Bucher U M, Richter J C

出版信息

Regul Pept. 1982 Nov;4(6):333-9. doi: 10.1016/0167-0115(82)90144-6.

DOI:10.1016/0167-0115(82)90144-6
PMID:6129682
Abstract

The time course of pancreatic effects of somatostatin was studied over a period of 2 h in unanesthetized unrestrained rats after administration of the peptide by intravenous infusion and by single and multiple subcutaneous injections. During infusion of 10 and 30 micrograms/kg per min, somatostatin continuously suppressed plasma insulin and plasma glucagon. Plasma glucose was significantly increased at the lower dose, but not affected at the higher dose. Single subcutaneous injections of 0.3 and 3 mg/kg decreased plasma insulin and glucagon dose-dependently for 20-60 min without affecting plasma glucose. Multiple subcutaneous injections of somatostatin (one to four doses of 3 mg/kg, administered at intervals of 30 min) caused an initial decrease of plasma insulin (at 30 min), a rebound-increase at 60 and 90 min, and a final return to control values by 120 min. Plasma glucagon remained continuously suppressed. Plasma glucose increased significantly at 60 and 90 min and tended to return towards control values thereafter. In conclusion, pancreatic B cells - but not A cells - of the rat develop tachyphylaxis to somatostatin within 2 h after multiple subcutaneous injections of the peptide. By this mode of administration, 'selective' suppression of plasma glucagon can be achieved with somatostatin in the rat.

摘要

在未麻醉、不受限制的大鼠中,通过静脉输注以及单次和多次皮下注射给予生长抑素后,在2小时内研究了其对胰腺作用的时间进程。在以每分钟10和30微克/千克的速度输注期间,生长抑素持续抑制血浆胰岛素和血浆胰高血糖素。较低剂量时血浆葡萄糖显著升高,但较高剂量时未受影响。单次皮下注射0.3和3毫克/千克可使血浆胰岛素和胰高血糖素剂量依赖性降低20 - 60分钟,而不影响血浆葡萄糖。多次皮下注射生长抑素(一至四剂3毫克/千克,间隔30分钟给药)导致血浆胰岛素最初下降(30分钟时),60和90分钟时出现反跳性升高,到120分钟时最终恢复到对照值。血浆胰高血糖素持续受到抑制。血浆葡萄糖在60和90分钟时显著升高,此后趋于恢复到对照值。总之,大鼠胰腺的B细胞——而非A细胞——在多次皮下注射该肽后2小时内对生长抑素产生快速耐受性。通过这种给药方式,生长抑素在大鼠中可实现对血浆胰高血糖素的“选择性”抑制。

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